Use of 19 nor dhea derivatives for enhancing physical performance

ABSTRACT

A method is disclosed for administering a DHEA derivative or a physiologically acceptable salt, ester or ether thereof for one of decreasing body weight, reducing adipose tissue, increasing endurance, as an anti-aging compound and generating production of red blood cells.

RELATED APPLICATIONS

This application claims priority benefit of U.S. provisional patentapplications No. 60/674,525, filed on Apr. 26, 2005, No. 60/694,813filed Jun. 29, 2005, and No. 60/762,328 filed Jan. 26, 2006.

FIELD OF THE INVENTION

This invention relates to use of derivatives of dehydroepiandrosterone(3-beta-hydroxy-5-androst-1-en-17-one or simply “DHEA”) to enhancephysical performance, and more particularly to the use of DHEAderivatives for anti-aging benefits, decreasing body weight, reducingadipose tissue, and increasing endurance.

BACKGROUND OF THE INVENTION

The adrenal gland produces many steroid hormones. These steroid hormonesplay a major role in many body processes including, for example,skeletal muscle growth, red blood cell production (erythropoiesis),regulation of glucose and insulin levels and cellular aging. Thesteroids produced by the adrenal gland can be divided into three groups:glucocorticoids, which influence carbohydrate metabolism;mineralocorticoids, which control electrolyte and water balance; and sexsteroid hormones. Glucocorticoids such as cortisol regulate catabolismof skeletal muscle proteins into amino acids. These amino acids are thentransported to the liver and converted into glucose duringgluconeogenesis. Excessive amounts of glucocorticoids can result inhigher blood glucose and insulin levels and can contribute to increasedbody fat and type II diabetes. Glucocorticoids are also known to play arole in the aging process by increasing cellular and mitochondrialbreakdown.

The second group of adrenal steroids, the mineralocorticoids such asaldosterone help the body to retain sodium and water. Excesses ofmineralocorticoids can result in hypertension and cardiovasculardisease.

The third group of adrenal steroids include androgens and DHEA. Adrenalandrogens oppose the actions of glucocorticoids and result in skeletalmuscle anabolism (the opposite action of catabolism), reductions inblood glucose and insulin levels, reduction in body fat, and arebelieved to decrease the rate of cellular aging and increased red bloodcell production. DHEA production by the adrenal glands is known todecline markedly as aging progresses.

With normal younger adults, all three groups of adrenal steroids areproduced in a healthy balance. However, as people age, less DHEA isproduced resulting in relatively greater amounts of glucocorticoids andmineralocorticoids and disruption of this balance.

DHEA supplementation is believed be useful in treatment of aging andobesity and to stimulate erythropoiesis and skeletal muscle anabolism.In addition, supplemental DHEA can help restore the balance of adrenalsteroids.

DHEA is commonly used as a dietary supplement. Unfortunately, DHEA israpidly metabolized by liver enzymes referred to as sulfotransferases.Sulfotransferases rapidly convert the much of the supplementary DHEAinto DHEA sulfate, which is quickly excreted from the body and is noteffective as an anti-aging, muscle-building or fat reduction compound.In addition, DHEA sulfate does not restore the balance of the adrenalsteroids discussed above. As a result, frequent and larger doses of DHEAmust be taken.

DHEA is also metabolized in the body to one of several compoundsincluding, for example, etiocholanolone(5-beta-androstan-3-alpha-ol-17-one), beta etiocholanolone(5-beta-androstan-3-beta-ol-17-one), androsterone(5-alpha-androstan-3-alpha-ol-17-one), epiandrosterone(5-alpha-androstan-3-beta-ol-17-one), 7-keto-DHEA, 7-alpha-hydroxy-DHEA,7-beta-hydroxy-DHEA, androstenedione, estrone and estradiol.

There is great individual variability in the metabolism of oral DHEA.The DHEA metabolites estrone and estradiol can result in negativeestrogenic side effects for males including growth of male breasttissue, known as gynecomastia. Some individuals have poorbioavailability of DHEA as a result of sulfation in the liver, and largedoses must be taken to elicit any desired effects. These increased dosesof DHEA can result in increased conversion to estrone and estradiol,with resulting negative side effects.

It would be desirable to provide compounds which can be used to helpprovide the beneficial effects of high DHEA levels in the body forextended periods of time, yet reduce the undesired DHEA side effectsdiscussed above.

SUMMARY OF THE INVENTION

In accordance with a first aspect, a method is disclosed foradministering a DHEA derivative or a physiologically acceptable salt,ester or ether thereof for decreasing body weight, reducing adiposetissue, increasing endurance, as an anti-aging compound and/orincreasing production of red blood cells.

From the foregoing disclosure and the following more detaileddescription of various preferred embodiments it will be apparent tothose skilled in the art that the present invention provides asignificant advance in the methods of administering anti-agingcompounds, for decreasing body weight and reducing adipose tissue, andincreasing endurance. Additional features and advantages of variouspreferred embodiments will be better understood in view of the detaileddescription provided below.

DETAILED DESCRIPTION OF CERTAIN PREFERRED EMBODIMENTS

It will be apparent to those skilled in the art, that is, to those whohave knowledge or experience in this area of technology that manyvariations are possible for the method of administering DHEA derivativesfor enhancing physical performance. The following detailed discussion ofvarious alternative and preferred features and embodiments willillustrate the general principles of the invention with reference toimproved methods of enhancing physical performance by administering DHEAderivatives as orally available dietary supplements. Other embodimentssuitable for other applications will be apparent to those skilled in theart given the benefit of this disclosure.

As used herein, a derivative of a compound refers to a species having achemical structure that is similar to the compound, yet containing achemical group not present in the compound and/or deficient of achemical group that is present in the compound. The substance to whichthe derivative is compared is known as the “parent” substance. Here, forexample, the parent compound is the androstane steroid DHEA. Aderivative may be made by modification of the parent compound or bysynthesis from other starting materials that are not similar to theparent.

DHEA derivatives disclosed herein are advantageous in that they lastlonger in the body and are resistant to conversion to estradiol andestrogen, thereby advantageously providing the benefits of supplementalDHEA (including anti-aging benefits, decreased body weight, reduction ofadipose tissue, increased endurance and/or increasing production of redblood cells) while reducing the negative side effects. Long-lasting DHEAderivatives are of the general formulas shown below, starting with theandrost-1ens:

wherein R3 is one of αOH, βOH, R5 is one of αH and βH, and R7 is one ofH and CH₃. DHEA derivatives made according to the above formula canconsist of 3-alpha-hydroxy-5-alpha-androst-1-en-17-one,3-beta-hydroxy-5-alpha-androst-1-en-17-one,3-alpha-hydroxy-5-alpha-7-alpha-methyl-androst-1-en-17-one,3-beta-hydroxy-5-alpha-7-alpha-methyl-androst-1-en-17-one,3-alpha-hydroxy-5-beta-androst-1-en-17-one,3-beta-hydroxy-5-beta-androst-1-en-17-one,3-alpha-hydroxy-5-beta-7-alpha-methyl-androst-1-en-17-one, and3-beta-hydroxy-5-beta-7-alpha-methyl-androst-1-en-17-one, along with anysalts, esters or ethers thereof.

Long lasting DHEA derivatives also include the following androst-4-ens:

wherein R3=one of is α-OH, β-OH. DHEA derivatives made according to theabove formula can consist of 3-beta-hydroxy-androst-4-en-17-one and3-alpha-hydroxy-androst-4-en-17-one along with any salts, esters orethers thereof.

Long lasting DHEA derivatives also include the androst-5-en compound:3-beta-hydroxy-7-alpha-methyl-androst-5-en-17-one, or any salts, estersor ethers thereof, reproduced immediately below:

Long lasting DHEA derivatives also include the androstan compound,3-alpha-hydroxy-5-alpha-androstan-7,17-dione, or any salts, esters orethers thereof, reproduced immediately below:

Long lasting DHEA derivatives also include 19-norandrost-4-en compoundsaccording to the general formula:

wherein R3=one of is α-OH, β-OH. DHEA derivatives made according to theabove formula can consist of 3-beta-hydroxy-norandrost-4-en-17-one and3-alpha-hydroxy-norandrost-4-en-17-one or any salts, esters or ethersthereof.

Long lasting DHEA derivatives also include 19-norandrost-5-en compoundsaccording to the general formula:

wherein R3=one of is α-OH, β-OH. DHEA derivatives made according to theabove formula can consist of 3-beta-hydroxy-norandrost-5-en-17-one and3-alpha-hydroxy-norandrost-5-en-17-one or any salts, esters or ethersthereof.

In accordance with conventional steroid carbon numbering, an atom orfunctional group attached to a ring depicted herein is termed α (alpha)if it lies below the plane of the paper or β (beta) if it lies above theplane of the paper. When R3 and/or R7 have one functional group listed,it is understood that the fourth bond to the carbon is hydrogen. Otherrelated DHEA derivatives suitable for administering anti-agingcompounds, for decreasing body weight and reducing adipose tissue, forincreasing production of red blood cells and/or increasing endurancewill be readily apparent to those skilled in the art, given the benefitof this disclosure.

All of the naturally occurring DHEA derivative compounds disclosedherein would preferably be administered orally mixed with solid orliquid carriers in appropriate unit doses.

The preferred amount of the active ingredient that is to beadministered, would depend on various factors such as the age and weightof the user. An effective oral daily dosage of the described DHEAderivatives can comprise 50-2000 mg daily, and most preferably about100-800 mg daily. A preferred embodiment might be to administer the oraldose as a soft gelatin capsule or oral liquid suspension, either in twoto three divided doses per day (i.e., 50 to 400 mg twice per day, or 25mg to 200 mg four times per day), The DHEA derivatives as disclosedherein may also be administered transdermally using acceptable liquidvehicles, sublingually, transrectally (by suppository) intranasally,intravenously, subcutaneously, or by intramuscular injection. The DHEAderivatives as disclosed herein may also be mixed with dietarysupplements such as creatine if desired.

EXAMPLE 1

Capsules. 1 kg of the DHEA derivative,3-beta-hydroxy-norandrost-4-en-17-one is mixed with microcrystallinecellulose, and placed into 10,000 hard-gelatin capsules. Each capsulecontains 100 mg of 3-beta-hydroxy-norandrost-4-en-17-one.

EXAMPLE 2

Capsules. 1 kg of the DHEA derivative3-beta-hydroxy-norandrost-5-en-17-one is mixed with 5 kg of creatine andplaced into 10,000 hard-gelatin capsules. Each capsule contains 100 mgof 3-beta-hydroxy-norandrost-5-en-17-one and 500 mg creatine.

From the foregoing disclosure and detailed description of certainpreferred embodiments, it will be apparent that various modifications,additions and other alternative embodiments are possible withoutdeparting from the true scope and spirit of the invention. Theembodiments discussed were chosen and described to provide the bestillustration of the principles of the invention and its practicalapplication to thereby enable one of ordinary skill in the art to usethe invention in various embodiments and with various modifications asare suited to the particular use contemplated. All such modificationsand variations are within the scope of the invention as determined bythe appended claims when interpreted in accordance with the breadth towhich they are fairly, legally, and equitably entitled.

1. (canceled)
 2. The method of claim 29 wherein the DHEA derivative isadministered in one of the following ways: orally, transdermally,intranasally, by injection, sublingually, and transrectally.
 3. Themethod of claim 29 wherein the DHEA derivative is administered as adaily dosage between about 50 mg and 2000 mg.
 4. The method of claim 29wherein the DHEA derivative is administered as a daily dosage betweenabout 100 mg and 400 mg.
 5. The method of claim 29 wherein the DHEAderivative is administered as a daily dosage between about 50 mg to 200mg twice per day.
 6. The method of claim 29 wherein the DHEA derivativeis administered as a daily dosage between about 25 mg to 100 mg fourtimes per day.
 7. The method of claim 29 wherein the DHEA derivative isadministered in the form of a gel capsule.
 8. The method of claim 29further comprising administering the DHEA derivative with creatine.9-28. (canceled)
 29. A method of administering a DHEA derivative or aphysiologically acceptable salt, ester or ether thereof as a compoundthat provides at least one of anti-aging adrenal hormonal balance,decreased body weight, reduction of adipose tissue, increased endurance,skeletal muscle growth, and increased production of red blood cells, ofthe general formula:

wherein R3 is one of α-OH and β-OH.